Treatment Of Mucosal Melanoma Research Articles

Comparative Epigenetic Profiling Reveals Distinct Features of Mucosal Melanomas Associated with Immune Cell Infiltration and Their Clinical Implications.

Mucosal melanoma exhibits limited responsiveness to anti-PD-1 therapy. However, a subgroup of mucosal melanomas, particularly those situated at specific anatomical sites like primary malignant melanoma of the esophagus (PMME), display remarkable sensitivity to anti-PD-1 treatment. The underlying mechanisms driving this superior response and the DNA methylation patterns in mucosal melanoma have not been thoroughly investigated. We collected tumor samples from 50 mucosal melanoma patients, including 31 PMME and 19 non-esophageal mucosal melanoma (NEMM). Targeted bisulfite sequencing was conducted to characterize the DNA methylation landscape of mucosal melanoma and explore the epigenetic profiling differences between PMME and NEMM. Bulk RNA sequencing and multiplex immunofluorescence staining were performed to confirm the impact of methylation on gene expression and immune microenvironment. Our analysis revealed distinct epigenetic signatures that distinguish mucosal melanomas of different origins. Notably, PMME exhibited distinct epigenetic profiling characterized by a global hypermethylation alteration compared to NEMM. The prognostic model based on the methylation scores of a 7-DMR panel could effectively predict the overall survival of PMME patients and potentially serve as a prognostic factor. PMME displayed a substantial enrichment of immune-activating cells in contrast to NEMM. Furthermore, we observed hypermethylation of the TERT promoter in PMME, which correlated with heightened CD8+ T cell infiltration, and patients with hypermethylated TERT were likely to have improved responses to immunotherapy. Our results indicated that PMME shows a distinct methylation landscape compared with NEMM, and the epigenetic status of TERT might be used to estimate prognosis and direct anti-PD-1 treatment for mucosal melanoma.

ARTISTRY-6: Nemvaleukin alfa monotherapy in patients with advanced mucosal and cutaneous melanoma.

TPS9609 Background: Despite improved outcomes for melanoma patients with the introduction of checkpoint inhibitors (CPIs), ̃50% of patients do not respond. A subset of responders ultimately progress and have limited treatment options, underscoring a high unmet need for novel treatments with durable benefit. Patients with mucosal melanoma exhibit response rates and progression-free survival times ̃2 times lower than those with cutaneous melanoma. Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel, engineered cytokine that selectively binds the intermediate-affinity interleukin-2 receptor complex to preferentially activate CD8+ T and NK cells with minimal expansion of regulatory T cells. Nemvaleukin has been granted Orphan Drug designation for the treatment of mucosal melanoma by the FDA. In ARTISTRY-1, the intravenous (IV) recommended phase 2 dose (RP2D) of 6 µg/kg nemvaleukin monotherapy demonstrated durable antitumor activity in patients with advanced melanoma, including mucosal melanoma, previously treated with a CPI. In ARTISTRY-2, the subcutaneous (SC) RP2D of 3 mg q7d was identified demonstrating pharmacodynamic effects consistent with IV delivery. Data support further evaluation of nemvaleukin monotherapy among patients with advanced mucosal and cutaneous melanoma. Methods: ARTISTRY-6 is a phase 2, global, multicenter, open-label study. Eligible patients have had prior treatment with an anti–PD-(L)1 therapy with or without anti–CTLA-4 therapy and have an ECOG performance status of 0 or 1 and adequate hematologic reserve and hepatic and renal function. Patients with advanced cutaneous (Cohort 1) and mucosal (Cohort 2) melanoma will receive nemvaleukin at the SC and IV RP2D, respectively. Patients will receive nemvaleukin until progression or intolerable toxicity. The primary objective is to evaluate the antitumor activity of nemvaleukin monotherapy defined by overall response rate. Additional objectives include the evaluation of safety, health-related quality of life, predictive biomarkers, pharmacokinetics, immunogenicity, and pharmacodynamic effects. Clinical trial information: NCT04830124.

Mucosal melanoma of the oral cavity

Primary mucosal melanomas of the head and neck region are uncommon but aggressive malignancies. These lesions arise from melanocytes located in mucosal membranes, predominantly in the nasal cavity, paranasal sinuses, and oral cavity. Mucosal melanomas account for less than 4% of all melanoma cases and are often missed, due to their occult initial presentations. This is in contrast to cutaneous melanomas, which constitute approximately 85% of melanoma cases and present on surfaces exposed to ultraviolet (UV) radiation. The mainstay of treatment for mucosal melanoma is surgical resection with adjuvant radiotherapy for patients with high-risk features. Despite advancements in surgical techniques, radiotherapy, and even systemic therapies, patients with mucosal melanoma face unfavourable prognoses (5-year disease-free survival <25%) with high rates of locoregional recurrence and/or distant metastases. The present case addresses a 47 year-old man who presents to Otolaryngology with an apparent mucosal melanoma involving the upper lip. This patient was informed of a pigmented lesion on the mucosal surface of the upper left lip three years prior by his dentist. Although largely asymptomatic, the lesion has increased in size. The patient undergoes surgical resection with clear margins and reconstruction. He continues to follow-up to monitor for disease recurrence, having denied adjuvant radiation. This case illustrates the diagnosis and approach to mucosal melanomas and highlights some of the key distinctions between mucosal and cutaneous melanomas.

Management and treatment of mucosal melanoma of the genital tract.

The melanoma of the genital mucosa is a rare melanocytic neoplasm that affects both sexes. The diagnosis is often delayed; videodermatoscopy may represent a useful diagnostic tool. The treatment is complex and multidisciplinary. We report the main diagnostic features and therapeutic approaches for mucosal melanoma of the genital tract.

Epidemiology, Clinical Presentation and Treatment of Mucosal Melanoma

Epidemiology, Clinical Presentation and Treatment of Mucosal Melanoma

PO-166: Special aspects of surgical treatment of mucosal melanoma affecting oral and nasal cavities

PO-166: Special aspects of surgical treatment of mucosal melanoma affecting oral and nasal cavities

Chemotherapy, biochemotherapy and anti-VEGF therapy in metastatic mucosal melanoma.

Mucosal melanomas arise from melanocytes located at various mucosal membranes, which demonstrate a clear demographic and ethnic disparity. This subtype of melanoma has more aggressive course and poorer prognosis than other subsets of melanomas. Due to their rarity, there is no well-established protocol of staging and treatment of mucosal melanomas. Significant advances have been achieved in novel immunotherapeutic and specific targeted agents for metastatic melanomas. For mucosal melanoma patients especially without known gene mutation, anti-angiogenic therapy combined with chemotherapy or other targeted drugs has shown promising efficacy, either as first- or second-line treatment. In some subset analysis, patients with mucosal melanoma, harboring wild type BRAF, might get more clinical and survival benefits than cutaneous ones. Therefore it is rational to further study these therapeutic strategies in the group of mucosal melanoma. Chemotherapy or biochemotherapy only showed limited efficacy without significant survival improvement, but larger sample size study is still required. Herein we presented a comprehensive review of chemotherapy/biochemotherapy and anti-vascular endothelial growth factor (anti-VEGF) therapy in metastatic mucosal melanoma.

Surgical Decision Making in Oral Mucosal Melanoma with Lymphadenopathy: Review of Literature

ABSTRACT The oral mucosal melanoma (OMM) comprises less than 1% of all malignant melanomas. Most mucosal melanomas occur in occult site, which together with lack of early and specific signs contribute to late and poor diagnosis. Because of their rareness, the knowledge about their pathogenesis and risk factors is insufficient, and also there are not well-established protocols for staging and treatment of mucosal melanomas with lymphadenopathy. Surgery is the mainstay of treatment. Radiotherapy and other adjunctive therapies can provide better local control in some locations, but did not show improvement in survival. In this article, we present a case of 52-year-old female with OMM (excision performed elsewhere) presenting with large left upper cervical swelling after 2 years postexcision. We will review the literature that help us in taking decision in the management of OMMs in light of following patient. How to cite this article Bakshi N, Mukherjee S, Chauhan YS. Surgical Decision Making in Oral Mucosal Melanoma with Lymphadenopathy: Review of Literature. Int J Head Neck Surg 2014;5(3):135-139.

PP170: Functional reconstruction after subtotal glossectomy in the surgical treatment of an uncommon and aggressive neoplasm in this location: Primary malignant melanoma in the base of the tongue

Purpose Primary malignant melanoma in oral cavity is rare neoplasm (according literature about 0.2–8% of the total of these tumors). In the oral cavity, they appear with more frequency in maxillary gingiva, palate mucosa and lips. However, primary malignant melanoma is specifically uncommon in the tongue. In the literature, only about 30 cases have been reported. The aim of this work is to show the functional reconstructive treatment after subtotal glossectomy due a rare and aggressive tumor. Materials and methods A 51-year-old man was referred to our department due to an asymptomatic pigmented lesion in the base of the tongue. On examination, a black, pigmented and diffuse mass measuring approximately 3 cm in size was found on the base of the tongue. There was no significant cervical lymphadenopathy. Biopsy of the tongue lesion revealed a histopathology consistent with primary malignant melanoma. Whole-body Computed Tomography (CT scan) and Positron Emission Tomography (PET scan) does not revealed distant metastatic lesions. Patient was treated by preoperative tracheotomy, subtotal glossectomy and bilateral functional neck dissection. The defect was reconstructed by an anterolateral thigh microvascularized free flap. Surgical treatment was supplemented with adjuvant radiotherapy and chemotherapy. Results The histopathological findings revealed a malignant melanoma. The resection margin and base of the tumor were clear and no evidence of metastasis was found in the tissue of the functional neck dissection. The postoperative course was uneventful. At present, one year after surgery, patient is asymptomatic, there isn’t evidence of recurrence of melanoma and he has not any difficulty in swallowing or phonation. Conclusions Melanomas in the tongue are rare neoplasms. Treatment of mucosal melanomas should be aggressive, due to their poor prognosis. Nevertheless, it’s possible the functional reconstructive treatment that preserves swallowing or phonation. For this, microsurgical reconstruction with anterolateral thigh free flap is an adequate option.

Sinonasal Mucosal Melanoma: An Enigma

Objective: To report two cases of mucosal melanoma of the sinonasal cavity from India and
 review the literature emphasizing current important clinical and biologic aspects of this tumor.
 
 Methods:
 Design: Case Report
 Setting: Tertiary Public Referral Hospital
 Patients: Two
 
 Results: Two patients presenting with progressive unilateral nasal obstruction over three to six
 months, respectively, were diagnosed to have sinonasal mucosal melanoma. The mass involved
 the nasal cavity and maxillary antrum in both patients. The first patient deferred radiotherapy for
 four months until pulmonary metastasis became evident, necessitating palliative chemotherapy;
 the second patient underwent surgical excision and radiotherapy.
 
 Conclusion: In spite of aggressive therapy, the prognosis for people with mucosal melanoma
 is extremely poor. Surgery remains the mainstay of treatment, although adjuvant radiation
 therapy has recently had an increasing role in the treatment of mucosal melanoma. A clear
 understanding of the pathophysiology of this disease may yield more specific immunotherapy
 and chemotherapy techniques. A multicenter prospective study is required to objectively assess
 the optimal treatment regimen.
 
 Keywords: mucosal melanoma, sinonasal cavity

687 poster Radiotherapy in the treatment of mucosal melanoma of the upper aero-digestive tract. A rare cancer network study

687 poster Radiotherapy in the treatment of mucosal melanoma of the upper aero-digestive tract. A rare cancer network study

Natural history and treatment of mucosal melanoma.

Forty-three patients with primary mucosal melanomas seen between 1960 and 1987 were reviewed. There were 17 patients with tumors arising from the head and neck, 17 from the vulva and/or vagina, 8 from the anorectum, and 1 from the esophagus. Twenty-one patients were resected with curative intent. In patients with head and neck tumors, local recurrence was the initial cause of failure in the majority of cases, whereas with tumors arising from the anorectum, vulva, and vagina, systemic recurrence was more common. There were four long-term survivors, and three of these had melanomas less than 1 mm thick with negative regional lymph nodes; no patients with mucosal melanoma less than 1 mm thick developed recurrent disease. Overall, actuarial survival was 64% after 1 year and 23% after 5 years. Mucosal melanoma has a poor prognosis, and adequate resectional surgery affords the only chance of long-term survival.